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Objective: YKL-40 is produced by macrophages, and plasma YKL-40 is elevated in patients with diseases characterized by inflammation. In the present study, YKL-40 was examined in relation to obesity, inflammation, and type 2 diabetes.Research Design and Methods: Plasma YKL-40 and adipose tissue YKL-40 mRNA levels were investigated in 199 subjects who were divided into four groups depending on the presence or absence of type 2 diabetes and obesity. In addition, plasma YKL-40 was examined in healthy subjects during a hyperglycemic clamp, in which the plasma glucose level was kept at 15 mmol/l for 3 h, and during a hyperinsulinemic-euglycemic clamp.Results: Patients with type 2 diabetes had higher plasma YKL-40 (76.7 vs. 45.1 ng/ml, P = 0.0001) but not higher expression in adipose tissue YKL-40 mRNA (1.20 vs. 0.98, P = 0.2) compared with subjects with a normal glucose tolerance. Within the groups with normal glucose tolerance and type 2 diabetes, obesity subgroups showed no difference with respect to either plasma YKL-40 or adipose tissue YKL-40 mRNA levels. Multivariate regression analysis showed that plasma YKL-40 was associated with fasting plasma glucose (beta = 0.5, P = 0.0014) and plasma interleukin (IL)-6 (beta = 0.2, P = 0.0303). Plasma YKL-40 was not related to parameters of obesity. There were no changes in plasma YKL-40 in healthy subjects during either hyperglycemic or hyperinsulinemic-euglycemic clamps.Conclusions: Plasma YKL-40 was identified as an obesity-independent marker of type 2 diabetes related to fasting plasma glucose and plasma IL-6 levels. [ABSTRACT FROM AUTHOR] more...

Background The optimal therapy for mucinous neoplasms of the pancreas is surgical resection because these tumours are either premalignant (cystadenoma) or malignant. Case outline A 44-year-old previously fit woman presented with sudden onset of epigastric pain. Clinical and laboratory findings were consistent with acute pancreatitis. Abdominal ultrasound scan demonstrated a mature 6-cm cyst in the tail of pancreas and no findings suggestive of cholelithiasis. These findings were confirmed by a CT scan, which also demonstrated splenic infarction and evidence of recent haemorrhage into the cyst. The patient's abdominal pain persisted after amylase levels returned to normal. Results Splenic infarction, a mature cyst in the tail of the pancreas, and peripancreatic inflammation consistent with recent pancreatitis were found at laparotomy. Enbloc distal pancreatectomy and splenectomy were performed. Histological examination of the cyst wall demonstrated a focus of mucinous cystadenoma. Discussion This case demonstrates that acute pancreatitis may be the first presentation of a cystic neoplasm. [ABSTRACT FROM AUTHOR] more...

Infection with Borrelia burgdorferi spirochetes can cause Lyme neuroborreliosis (LNB). Neuroborreliosis presenting as encephalitis is a rare manifestation. We present a 72-year-old male patient hospitalized after three days of confusion and altered mental status. Initial computerized tomography (CT) and magnetic resonance imaging (MRI) of the brain were both unremarkable. Lumbar puncture showed an elevated number of white blood cells, elevated protein, and normal glucose levels in the cerebrospinal fluid (CSF), normal electroencephalogram (EEG), and negative tests for common microorganisms in the CSF. The patient received treatment with acyclovir and ceftriaxone. Lumbar puncture repeated on day 16 showed a decreasing number of white blood cells. A repeated MRI showed white matter edema, interpreted as encephalitis, while a repeated EEG showed signs of a non-specific cerebral lesion. The first lumbar puncture revealed intrathecal immunoglobulin M (IgM) antibodies against  Borrelia  and was positive for Borrelia DNA using real-time PCR, and the following lumbar puncture showed both IgM and IgG intrathecal antibody production. These results thus confirmed the diagnosis of Lyme  Borrelia  encephalitis. The patient improved clinically and was discharged after treatment with ceftriaxone for three weeks. Encephalitis due to LNB should be considered as a differential diagnosis in cases with unexplained neurological symptoms. Changes in MRI and/or EEG might occur late in the course of the disease, underlining the need for repeated tests in unresolved cases., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, David Ruban et al.) more...

Objective: The purpose of this report was to describe a patient with a Pancoast tumor who presented for chiropractic care with neck and arm pain., Clinical Features: A 52-year-old male patient with right-sided cervicothoracic pain and numbness in the right upper extremity presented to a chiropractic office for care. The patient reported an occupational history of repetitive lifting motions and overuse injuries. The patient denied history of smoking at the time of presentation., Intervention and Outcome: Radiographic imaging revealed tracheal deviation. A chest computed tomography image demonstrated a large lesion in the apex of the right lung, suggestive of bronchogenic carcinoma. The patient was referred to an oncology clinic, where he admitted to having a 20-year history of smoking. The diagnosis of adenocarcinoma was made via biopsy, and the oncologist's evaluation confirmed the cancer to be stage IIIC. The patient received palliative care treatments, as the advanced state of his condition determined that he was not a candidate for surgical intervention., Conclusion: Chiropractors and other first-contact health care providers must keep in mind unusual presentations masquerading as common conditions. This case demonstrates the importance of including apical lung tumors in the differential diagnosis of unilateral arm and neck pain and neurologic deficits of the upper extremity. This case demonstrates the importance of thorough follow-up on images ordered, including the ordering clinicians viewing the images themselves., (© 2023 by National University of Health Sciences.) more...

Objectives: To identify factors associated with antibiotic treatment delay in patients admitted with bloodstream infections (BSIs)., Design: Retrospective cohort study., Setting: North Zealand Hospital, Denmark., Patients: Adult patients with positive blood cultures obtained within the first 48 hours of admission between January 1, 2015, and December 31, 2015 ( n = 926)., Measurements and Main Results: First recorded Early Warning Score (EWS), patient characteristics, time to antibiotic treatment, and survival at day 60 after admission were obtained from electronic health records and medicine module. Presence of contaminants and the match between the antibiotic treatment and susceptibility of the cultured microorganism were included in the analysis. Data were stratified according to EWS quartiles. Overall, time from admission to prescription of antibiotic treatment was 3.7 (3.4-4.0) hours, whereas time from admission to antibiotic treatment was 5.7 (5.4-6.1) hours. A gap between prescription and administration of antibiotic treatment was present across all EWS quartiles. Importantly, 23.4% of patients admitted with BSI presented with an initial EWS 0-1. Within this group of patients, time to antibiotic treatment was markedly higher among nonsurvivors at day 60 compared with survivors. Furthermore, time to antibiotic treatment later than 6 hours was associated with increased mortality at day 60. Among patients with an initial EWS of 0-1, 51.3% of survivors received antibiotic treatment within 6 hours, whereas only 19.0% of nonsurvivors received antibiotic treatment within 6 hours., Conclusions: Among patients with initial low EWS, delay in antibiotic treatment of BSIs was associated with increased mortality at day 60. Lag from prescription to administration may contribute to delayed antibiotic treatment. A more frequent reevaluation of patients with infections with a low initial EWS and reduction of time from prescription to administration may reduce the time to antibiotic treatment, thus potentially improving survival., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.) more...

Objective: To bridge the gap between evidence and clinical judgement, we defined scenarios appropriate for ureteral stent omission after uncomplicated ureteroscopy (URS) using the RAND/UCLA Appropriateness Method (RAM). We retrospectively assessed rates of appropriate stent omission, with the goal to implement these criteria in clinical practice., Methods: A panel of 15 urologists from the Michigan Urological Surgery Improvement Collaborative (MUSIC) met to define uncomplicated URS and the variables that influence stent omission decision-making. Over two rounds, they scored clinical scenarios for Appropriateness Criteria (AC) for stent omission based on a combination of variables. AC were defined by median scores: 1 to 3 (inappropriate), 4 to 6 (uncertain), and 7 to 9 (appropriate). Multivariable analysis determined the association of each variable with AC scores. Uncomplicated URS cases in the MUSIC registry were assigned AC scores and stenting rates assessed., Results: Seven variables affecting stent decision-making were identified. Of the 144 scenarios, 26 (18%) were appropriate, 88 (61%) inappropriate, and 30 (21%) uncertain for stent omission. Most scenarios appropriate for omission were pre-stented (81%). Scenarios with ureteral access sheath or stones >10mm were only appropriate if pre-stented. Stenting rates of 5,181 URS cases correlated with AC scores. Stents were placed in 61% of cases appropriate for omission (practice range, 25% to 98%)., Conclusion: We defined objective variables and AC for stent omission following uncomplicated URS. AC scores correlated with stenting rates but there was substantial practice variation. Our findings demonstrate that the appropriate use of stent omission is underutilized. more...

Purpose: In clinically node-positive breast cancer, axillary staging after neoadjuvant chemotherapy (NAC) is optimized with targeted axillary dissection (TAD), which includes removal of the biopsy-proven metastatic lymph node (LN) in addition to sentinel lymph nodes (SLN). Localization of the clipped node is currently performed post-NAC; however, technical limitations can make detection and localization of the treated LN challenging. We prospectively evaluated the feasibility of localizing the metastatic LN with a SAVI SCOUT® reflector (SAVI) prior to NAC for targeted removal at surgery., Methods: Twenty-five patients with stage 2/3 breast cancer underwent ultrasound-guided localization of the biopsy-proven LN with SAVI prior to NAC. After NAC, patients with clinical response underwent TAD. Primary outcome measures were rate of successful localization, days between insertion of SAVI and axillary surgery, frequency of retrieval of clipped node, and frequency of SAVI-LN as SLN., Results: After NAC, 23/25 (92%) had clinical axillary down-staging and underwent TAD. Two patients with persistent palpable axillary disease underwent ALND for initial staging. Axillary surgery was performed at an average of 141 days post-SAVI insertion and the SAVI was successfully retrieved in all cases. Among 23 patients undergoing TAD, the SAVI was retrieved within a LN in all patients, whereas clip migration was observed in two patients. The median SLN removed was 4, and SAVI-LN was SLN in 22/23 patients. Axillary pCR rate was 44%., Conclusion: Localizing a metastatic LN with SAVI reflector prior to NAC for targeted removal at surgery is feasible and may provide technical and logistical advantages over axillary localization post-NAC., Clinical Trial Registry: Clinical trials.gov identifier: NCT03411070., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) more...

After decades of experience supporting surgical quality and safety by the American College of Surgeons, the American College of Surgeons Quality Verification Program was developed to help hospitals improve surgical quality, safety, and reliability. This review is the second of a 3-part review aiming to synthesize the evidence supporting the main principles of the American College of Surgeons Quality Verification Program. Evidence was systematically reviewed for 5 principles: case review, peer review, credentialing and privileging, data for surveillance, and continuous quality improvement using data. MEDLINE was searched for articles published from inception to January 2019 and 2 reviewers independently screened studies for inclusion in a hierarchical fashion, extracted data, and summarized results in a narrative fashion. A total of 9,098 studies across the 5 principles were identified. After exclusion criteria, a total of 184 studies in systematic reviews and primary studies were included for assessment. The identified literature supports the importance of standardized processes and systems to identify problems and improve quality of care., (Copyright © 2021 American College of Surgeons. Published by Elsevier Inc. All rights reserved.) more...

Acquisition of data on clinical performance is essential to improve outcomes in surgery. Large, national datasets allow hospitals to monitor events involving patient safety, complications, and benchmark against peer hospitals and facilitate quality improvement (QI) development. Although clinical datasets are often preferable, administrative data also have potential for actionable QI. Hospitals should use whatever data resources may be available and be creative in combining data sources for the most clinically meaningful metrics. Although collection of data is essential in understanding the problems an individual hospital is facing, rigorous QI infrastructure is necessary to translate data to action and achieve sustained change., Competing Interests: Disclosures B.C. Brajcich and C.P. Fischer have no disclosures, financial or otherwise, to report. C.Y. Ko is the Director of the American College of Surgeons Division of Research and Optimal Patient Care., (Copyright © 2020 Elsevier Inc. All rights reserved.) more...

Background: Emergency colorectal operations account for considerable surgical morbidity, leading to increased recognition of the importance of standardized care. Enhanced recovery pathways (ERPs) have successfully provided a framework to standardize elective surgical care, with some ERP elements spreading to emergency procedures. This study aims to characterize the degree of spread and demonstrate feasibility of ERP extension to emergency colorectal operations., Study Design: Patients undergoing colorectal operations were identified from a national ERP collaborative. Adherence to ERP process measures-multimodal pain control, early Foley removal, postoperative venous thromboembolism prophylaxis, early mobilization, early feeding, and 30-day clinical outcomes-was analyzed. Multivariable logistic regression was used to evaluate association between process measure adherence and 30-day clinical outcomes., Results: A total of 31,511 patients underwent colorectal operations at 235 hospitals; 3,086 were emergencies and 28,425 were elective. For emergency cases, rates of early Foley removal (92.0%) and venous thromboembolism prophylaxis (75.7%) were highest. Rates of multimodal pain control (55.9%), early mobilization (37.1%), and early liquid intake (33.4%) were modest. Nonadherence was more common in patients younger than 65 years (43.4%), with independent functional status (94%), American Society of Anesthesiologists Physical Status Classification 1 to 3 (62.5%), and without physiologic derangement (39.9%). Lack of mobilization or liquid intake was independently associated with increased odds of ileus (odds ratio [OR] 1.43; 95% CI, 1.18 to 1.75 and OR 2.41; 95% CI, 1.96 to 2.95) and prolonged length of stay (OR 2.29; 95% CI, 1.85 to 2.83 and OR 2.05; 95% CI, 1.70 to 2.47)., Conclusions: Although the unplanned nature of emergency colorectal operations historically excluded patients from ERPs, our findings suggest ERPs have observable diffusion beyond elective surgical procedures. Deliberate implementation with adherence auditing can improve ERP uptake and outcomes in emergency colorectal operations., (Copyright © 2020 American College of Surgeons. All rights reserved.) more...

Wild animals brought into captivity frequently experience chronic stress and typically need a period of time to adjust to the conditions of captivity (restraint, artificial lighting, altered diet, human presence, etc.), to which they may never fully acclimate. Changes in mass, the hypothalamic-pituitary-adrenal axis and heart rate parameters have been observed over the first week in newly captive house sparrows ( Passer domesticus ). In this study, we tested the effects of two drugs, diazepam and mitotane, in preventing the chronic stress symptoms caused by captivity, compared with oil-injected control animals. Diazepam is an anxiolytic that is widely prescribed in humans and other animals and has been shown in some cases to reduce physiological stress. Mitotane is an agent that causes chemical adrenalectomy, reducing the body's capacity to produce glucocorticoid hormones. Our mitotane treatment did not cause the expected change in corticosterone concentrations. Baseline corticosterone was higher after a week in captivity regardless of the treatment group, while stress-induced corticosterone did not significantly increase above baseline after a week in captivity in any treatment group. However, mitotane treatment did have some physiological effects, as it reduced the resting heart rate and the duration of the heart rate response to a sudden noise. It also prevented the increase in nighttime activity that we observed in control animals. There was no effect of diazepam on corticosterone, resting heart rate, activity or heart rate response to a sudden noise, and no effect of either treatment on the sympathetic vs parasympathetic control of the resting heart rate. Together, these data suggest that mitotane, but not diazepam, can have a modest impact on helping house sparrows adapt to captive conditions. Easing the transition to captivity will likely make conservation efforts, such as initiating captive breeding programs, more successful., (© The Author(s) 2020. Published by Oxford University Press and the Society for Experimental Biology.) more...

Decades of quality program development by the American College of Surgeons (ACS) have identified the key components of a successful program for optimal surgical care and quality improvement. These key principles have been developed into a verification program-the ACS Quality Verification Program-to guide hospitals to improve surgical quality, safety, and reliability across all surgical specialties. The aim of this review was to synthesize the evidence supporting the first 4 of 12 ACS Quality Verification Program core principles of building quality and safety resources and infrastructure. MEDLINE was searched for articles published from inception to January 2019 for studies describing principles of leadership commitment to surgical quality and safety, a surgical quality officer, a surgical quality committee, and a culture of safety and high reliability. Two reviewers independently screened studies for inclusion in a hierarchical fashion, extracted data, and summarized results in a narrative fashion. A total of 5,332 studies across the 4 principles were identified. After exclusion criteria, a total of 477 studies in systematic reviews and primary studies were included for assessment. Despite heterogeneous study design and lack of randomized controlled trials, the available literature supports the importance of committed top-level hospital leadership, mid-level leadership, and committee dedicated to surgical quality and culture of safety and high reliability. In conclusion, adequate resources and infrastructure integral to the ACS Quality Verification Program are critical to achieving safe and high-quality surgical outcomes., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.) more...

Neophobia is a behavior characterized by a reluctance to approach novel objects. We measured neophobia in captive wild house sparrows (Passer domesticus) by comparing the time it took for hungry birds to approach their normal food dish compared to one that had been modified with a novel object. We tested the behavior of animals captured at different times of year to test for seasonal variation in neophobia. One group of birds tested in July approached their food dishes much more quickly than all other birds (a matter of seconds rather than minutes whether or not there was a novel object), a response that was not repeated in a subsequent July. When this possible outlier group was removed from the analysis, approach times to novel objects were not affected by season. However, animals captured and tested in October had a stronger motivation to feed (i.e., they approached unmodified food dishes faster) than birds captured at other times of the year. If we define "neophobia" as an increase in latency to approach a novel versus an unmodified food dish, then there is little evidence for underlying seasonal variation in risk assessment, although a general motivation to feed does show a seasonal pattern., (© 2020 Wiley Periodicals, Inc.) more...

Purpose: Multiple wire-free technologies for localization of non-palpable breast cancers have emerged as satisfactory alternatives to wire. However, no study has compared two non-radioactive wire-free approaches to one another. The purpose of this study was to compare outcomes among LOCalizer™ radiofrequency identification (RFID), SAVI Scout® (SAVI), and wire localization (WL)., Methods: This was a retrospective, cross-sectional cohort study of patients undergoing lumpectomy for non-palpable breast cancer at a single institution between August 2017 and February 2019. Patients were divided into three cohorts based on localization technique: RFID, SAVI or WL. Operative times and average tumor volumes were compared using one-way analysis of variance. Positive margin and re-excision rates were compared with Fisher's exact test., Results: Among 104 patients who underwent lumpectomy for non-palpable breast cancer, 33 patients (31.7%) had RFID, 21 (20.2%) had SAVI, and 50 (48.0%) had WL. Operative times were 79 min for RFID, 81 min for SAVI, and 78 min for WL (p = 0.91). Volume of tissue resected was 36.3 cm 3 , 31.7 cm 3 , and 35.3 cm 3 for RFID, SAVI, and WL, respectively (p = 0.84). Positive margin rates (RFID 3.0% vs SAVI 9.5% vs WL 8.0%, p = 0.67) and re-excision rates (RFID 6.1% vs SAVI 9.5% vs WL 10.0%, p = 0.82) were similar across groups., Conclusions: Wire-free localization technologies have been compared to WL demonstrating similar efficacy. Our study suggests that RFID and SAVI Scout also perform similarly to one another. Physicians and institutions may consider more nuanced features of each localization system rather than performance alone when choosing a wire-free alternative. more...

Wild animals are brought into captivity for many reasons-conservation, research, agriculture and the exotic pet trade. While the physical needs of animals are met in captivity, the conditions of confinement and exposure to humans can result in physiological stress. The stress response consists of the suite of hormonal and physiological reactions to help an animal survive potentially harmful stimuli. The adrenomedullary response results in increased heart rate and muscle tone (among other effects); elevated glucocorticoid (GC) hormones help to direct resources towards immediate survival. While these responses are adaptive, overexposure to stress can cause physiological problems, such as weight loss, changes to the immune system and decreased reproductive capacity. Many people who work with wild animals in captivity assume that they will eventually adjust to their new circumstances. However, captivity may have long-term or permanent impacts on physiology if the stress response is chronically activated. We reviewed the literature on the effects of introduction to captivity in wild-caught individuals on the physiological systems impacted by stress, particularly weight changes, GC regulation, adrenomedullary regulation and the immune and reproductive systems. This paper did not review studies on captive-born animals. Adjustment to captivity has been reported for some physiological systems in some species. However, for many species, permanent alterations to physiology may occur with captivity. For example, captive animals may have elevated GCs and/or reduced reproductive capacity compared to free-living animals even after months in captivity. Full adjustment to captivity may occur only in some species, and may be dependent on time of year or other variables. We discuss some of the methods that can be used to reduce chronic captivity stress., (© The Author(s) 2018. Published by Oxford University Press.) more...

Acute rises in glucocorticoid hormones allow individuals to adaptively respond to environmental challenges but may also have negative consequences, including oxidative stress. While the effects of chronic glucocorticoid exposure on oxidative stress have been well characterized, those of acute stress or glucocorticoid exposure have mostly been overlooked. We examined the relationship between acute stress exposure, glucocorticoids and oxidative stress in Japanese quail ( Coturnix japonica ). We (i) characterized the pattern of oxidative stress during an acute stressor in two phenotypically distinct breeds; (ii) determined whether corticosterone ingestion, in the absence of acute stress, increased oxidative stress, which we call glucocorticoid-induced oxidative stress (GiOS); and (iii) explored how prior experience to stressful events affected GiOS. Both breeds exhibited an increase in oxidative stress in response to an acute stressor. Importantly, in the absence of acute stress, ingesting corticosterone caused an acute rise in plasma corticosterone and oxidative stress. Lastly, birds exposed to no previous acute stress or numerous stressful events had high levels of GiOS in response to acute stress, while birds with moderate prior exposure did not. Together, these findings suggest that an acute stress response results in GiOS, but prior experience to stressors may modulate that oxidative cost. more...

Purpose: Use of a wire to localize a non-palpable breast lesion for surgery is standard but archaic. We sought to evaluate a new radiofrequency localization system (RFLS) as an effective, non-radioactive alternative to the wire., Methods: Patients who required surgical excision of a non-palpable breast lesion were consented for the study. Patients underwent localization with a radiofrequency Tag and surgical removal guided by the handheld LOCalizer probe. The primary study endpoint was successful placement and retrieval of the Tag, and secondary endpoints included marker migration; days prior to surgery of Tag insertion; patient, radiologist, and surgeon experience; distance of Tag from skin; and positive margin and re-excision rates for cancer., Results: Fifty patients had successful placement and retrieval of the radiofrequency Tag. Likert questionnaire data revealed that most patients thought the procedure went smoothly and was easier than expected. Radiologists and surgeons thought that the Tag was as reliable as the wire. Of the 33 patients who had surgery for in situ or invasive cancer, one had a positive margin on final pathology (3%) and two underwent re-excision (6%)., Conclusions: Data from this pilot study suggest that the RFLS is an effective localization system for non-palpable breast lesions intended for surgical removal. Unlike most other technologies, the LOCalizer probe detects distance from the Tag, and this unique feature may have contributed to the low positive margin rate seen in this study. The RFLS appears to offer advantages over current localization procedures and should be explored as an alternative to wire. ClinicalTrials.gov Identifier: NCT03202472. more...

Purpose: Advances in preimplantation genetic testing (PGT) have led to practice changes in assisted reproductive technologies (ART), enabling fertility centers to transfer single embryos while maintaining excellent ongoing pregnancy rates, reducing miscarriage rates, and dramatically reducing ART-associated multiple pregnancies. The introduction of next-generation sequencing (NGS) allows PGT laboratories to assess for embryo mosaicism-although the true incidence and reproductive potential of predicted mosaic embryos are controversial. Due to concern for genetic contamination from other spermatozoa, most reference laboratories require use of intracytoplasmic sperm injection (ICSI) for single gene preimplantation genetic diagnosis (PGT-M). However, in PGT for aneuploidy (PGT-A), conventional insemination (IVF) is typically permissible. The purpose of this study was to evaluate rates of euploid, aneuploid, and mosaic in trophectoderm biopsy samples from embryos in IVF versus ICSI PGT-A cycles. Secondary aims were to assess sex ratio, and subtypes of aneuploidy and mosaicism in IVF versus ICSI PGT-A cycles., Methods: We performed a retrospective review of women undergoing PGT-A at a single academic fertility center from July 1, 2015, to September 1, 2017. In all cycles, PGT-A was performed via trophectoderm biopsy on day 5 or 6 and analyzed using NGS at a single reference lab. We collected and compared patient demographics, fertility testing, cycle characteristics, and PGT-A outcomes between IVF and ICSI cycles., Results: Three hundred two PGT-A cycles were included for analysis: 75 IVF and 227 ICSI cycles, resulting in 251 IVF and 724 ICSI biopsied blastocysts. Mean oocyte age of included cycles was 38.6 years (IVF) and 38.5 years (ICSI), p = 0.85. Baseline characteristics of IVF and ICSI PGT-A cycles were similar with the exception of semen parameters: IVF cycles had higher sperm concentration and total motility compared to ICSI cycles. PGT-A outcomes did not differ between IVF and ICSI cycles: euploid 27.9% (IVF) versus 30% (ICSI); aneuploid 45.4% (IVF) versus 43.1% (ICSI); no result 4.4% (IVF) versus 6.2% (ICSI). Though not significant, we identified a trend toward higher rate of mosaicism in IVF (25.9%) versus ICSI (20.9%). Among mosaic embryos, a lower percentage of simple mosaic embryos resulted from IVF (53.8%) versus ICSI (70.2%). Among aneuploid embryos, a non-significant higher percentage of complex aneuploidy resulted from IVF (16.3%) versus ICSI (9%). IVF resulted in a non-significant higher proportion of cycles with no transferrable embryos (42.7%) versus ICSI (36.6%). Numerical and sex chromosome involvement in mosaicism and aneuploidy were similar between IVF and ICSI cycles., Conclusion: IVF and ICSI NGS PGT-A have similar rates of euploid, aneuploid, and no result embryos, though IVF may result in higher rates of mosaicism and demonstrates differences in proportions of mosaic and aneuploid subtypes compared to ICSI. ICSI may be preferable to conventional insemination to minimize the rate of mosaic results in NGS PGT-A cycles. more...

The conditions of captivity can cause chronic stress in wild animals. Newly-captured animals may experience weight loss, elevated glucocorticoid hormones, increased heart rate, increased resting adrenomedullary activation, and an altered heart rate response to acute stressors. As captivity conditions persist, chronic stress may decrease as animals adjust to the stressors of captivity. In this study, house sparrows (Passer domesticus) were captured from the wild, fitted with heart rate transmitters in a minor surgical process, and individually housed in an indoor bird facility. Mass, baseline corticosterone, resting heart rate, resting adrenomedullary activation, and the acute heart rate response to a sudden noise were measured over the course of the first 6 weeks of captivity. Birds lost weight during the first weeks of captivity, which was regained by week 5. Baseline corticosterone peaked at day 7, decreased sharply by day 11, and continued to decrease throughout the 6 weeks. Although heart rate in the first 24 h could not be collected, daytime heart rate decreased from day 1 through day 20, where it reached a stable plateau. Daytime heart rate variability decreased through the entire 6 weeks, which may indicate a gradual shift from sympathetic to parasympathetic nervous system regulation of heart rate. The acute heart rate response to a sudden noise lasted longer at day 6 than earlier or later in captivity. In conclusion, the data indicate that the different physiological systems associated with chronic stress adjust to captivity over different timelines., (Copyright © 2017 Elsevier Inc. All rights reserved.) more...

A clinical validation of the bone scan lesion area (BSLA) as a quantitative imaging biomarker was performed in metastatic castration-resistant prostate cancer (mCRPC). BSLA was computed from whole-body bone scintigraphy at baseline and week 12 posttreatment in a cohort of 198 mCRPC subjects (127 treated and 71 placebo) from a clinical trial involving a different drug from the initial biomarker development. BSLA computation involved automated image normalization, lesion segmentation, and summation of the total area of segmented lesions on bone scan AP and PA views as a measure of tumor burden. As a predictive biomarker, treated subjects with baseline BSLA [Formula: see text] had longer survival than those with higher BSLA ([Formula: see text] and [Formula: see text]). As a surrogate outcome biomarker, subjects were categorized as progressive disease (PD) if the BSLA increased by a prespecified 30% or more from baseline to week 12 and non-PD otherwise. Overall survival rates between PD and non-PD groups were statistically different ([Formula: see text] and [Formula: see text]). Subjects without PD at week 12 had longer survival than subjects with PD: median 398 days versus 280 days. BSLA has now been demonstrated to be an early surrogate outcome for overall survival in different prostate cancer drug treatments. more...

Objective: This pilot study tested a survey instrument pertaining to the instruction and assessment of tumor imaging in chiropractic training programs. The secondary purpose was to gather data regarding credentials of lead instructors, textbook and resource use, and tumors taught and assessed., Methods: An electronic survey was distributed to lead tumor imaging instructors at all chiropractic colleges in the United States and Canada. A focus group of tumor imaging instructors was conducted to clarify ambiguous data., Results: Diplomate status with the American Chiropractic Board of Radiology was held by 87.5% of the instructor respondents. There were similarities in course content and assessment across institutions. A total of 26 tumors were considered clinically significant by more than 65% of instructors, 9 tumors were identified as not clinically significant by more than 65%, and 4 tumors were considered clinically significant by 35% to 65% of instructors. There was correlation between those instructors who evaluated on various tumors and those who feel it is important to evaluate such tumors (r S = 0.94, p < .001). The focus group addressed the 4 equivocal tumors and recommended 3 be added to the list of clinically insignificant tumors., Conclusion: The survey instrument is ready to be used to conduct a study of all clinical areas of the chiropractic curriculum. A total of 12 tumors were recommended for removal from National Board of Chiropractic Examiners tests. The authors recommend that the Academics Committee of the American Chiropractic Board of Radiology share information regarding learning libraries to allow for a richer learning experience across all campuses. more...

When wild animals are brought into captivity for the first time, they frequently develop chronic stress symptoms. Animals can develop glucocorticoid dysregulation or changes in the sympathetic nervous system over the course of the first week in captivity. By blocking the action of epinephrine and norepinephrine using α- or β-blockers, we hoped to reduce the degree of chronic stress symptoms exhibited by newly captured house sparrows. We measured corticosterone, heart rate and heart rate variability in 24 house sparrows ( Passer domesticus ) over the first week of captivity. The birds were treated with saline, propranolol (a β-blocker) or phentolamine (an α-blocker) for the first 3 days of captivity. We also compared newly captured animals with animals that had been held in captivity for 1 month. During the first week of captivity, baseline corticosterone increased, but that increase was blocked by propranolol. Heart rate was not different between the treatment groups, but it was higher during the first week than after 1 month in captivity. Sympathetic nervous system activity (as measured by heart rate variability) decreased over the first week of captivity, but was not affected by treatment. β-Blockers, but not α-blockers, might help to improve some symptoms of chronic stress in newly captured animals. more...

Neophobia, or the fear of novel objects, is a behavior that is often found in wild animals. Neophobia appears to be related to the physiological stress response because individuals with higher glucocorticoid responses to stress often are more neophobic. The relationship between the heart rate response and novelty, however, has not been tested in a wild species. We implanted heart rate transmitters in captive European starlings (Sturnus vulgaris) to measure increases in heart rate as an index of the adrenomedullary stress response. Specifically, we measured heart rate in animals encountering novel objects on or near their food dishes using a system to display the novel objects while the experimenters remained outside the room, thereby minimizing the confounding effects of experimenter presence on heart rate. We analyzed three conditions: the period of adjustment to the experimental setup before any exposure to novelty, novel object trials, and no object controls (presented in a random order after 0-5 novel objects). Birds approached their food dishes faster during the adjustment period than during novel object trials. Although they demonstrated a behavioral aversion to novelty, the effect on heart rate was unexpected. Heart rate increased sharply when the food dishes were displayed. The duration of the startle response was longer during no object controls than during novel object exposure, the opposite of the anticipated result. There were no correlations between behavior and metrics of the heart rate response. Novel object exposure does not cause an increase in heart rate., (Copyright © 2016 Elsevier Inc. All rights reserved.) more...

Objective: The purpose of this report is to present a presumptive case of ankylosing spondylitis with late stage progression that simulated osteoblastic metastasis in a patient with a history of prostate carcinoma., Clinical Features: A 67-year-old white man presented to a chiropractic clinic complaining of severe and worsening acute low back pain and right foot "numbness." Further questioning also revealed a history of prostate carcinoma., Intervention and Outcome: Imaging examination revealed a sclerotic pedicle and increased uptake of radiopharmaceutical on a nuclear medicine bone scan highly suggestive of osteoblastic skeletal metastasis. Further evaluation, however, revealed that the bone sclerosis was not the result of skeletal metastasis, but more consistent with a seronegative spondyloarthritis such as ankylosing spondylitis., Conclusion: This report describes a presumptive case of ankylosing spondylitis simulating skeletal metastasis in a patient with a past medical history of prostate cancer. This atypical presentation illustrates the inherent uncertainty of diagnosis and how that uncertainty can be challenging in clinical practice. It also reinforces that it is critical for healthcare providers to consider a wide spectrum of differential diagnoses to avoid misdiagnoses and inappropriate interventions. more...

Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P<5.0E-08. These findings provide additional insight into the underlying biological mechanisms of colorectal cancer and demonstrate the scientific value of large consortia-based genetic epidemiology studies. more...

Background: The risk of life-threatening and invasive infections with encapsulated bacteria is increased in patients with hyposplenia or asplenia. We report a case of recurrent invasive pneumococcal meningitis in a woman with previous unknown hyposplenia. She was vaccinated after the first episode of meningitis and developed sufficient levels of pneumococcal antibodies. The pneumococcal strains isolated were serotype 7 F and 17 F. To our knowledge, there has been no previously reported case of recurrent invasive pneumococcal disease in a pneumococcal vaccinated adult with hyposplenia and apparently sufficient antibody response., Case Presentation: We report the course of a 38-year-old Caucasian woman presenting with recurrent episodes of invasive pneumococcal disease (IPD) and previously unknown hyposplenia. Hyposplenia was discovered during the second episode of IPD and no underlying medical condition was found. Despite immunization against S. pneumoniae and measurement of what was interpreted as protective levels of serotype-specific IgG antibodies after vaccination, the patient suffered from a third episode of IPD., Conclusions: Individuals with predisposing medical conditions or a history of severe infections with encapsulated bacteria should be screened for spleen dysfunction. If splenic function is impaired, prevention against severe invasive infection with encapsulated bacteria are a major priority. more...

Objective: The outcomes of patients with idiopathic pulmonary fibrosis (IPF) who undergo hospitalization have not been well characterized. We sought to determine the frequency of all-cause and respiratory-related hospitalizations and to evaluate their impact on the subsequent course and survival of patients with IPF., Methods: The records of patients with IPF evaluated at a tertiary center were examined for the cause and duration of hospitalization. Data on subsequent patient outcomes were collated., Results: The IPF cohort consisted of 592 patients, 25.3% of whom were hospitalized subsequent to their IPF diagnosis. A respiratory-related cause accounted for 77.3% of these hospitalizations. The median transplant-free survival for all patients was 23.3 months (interquartile range [IQR], 7.6-63.6 months) from the time of consultation. Transplant-free survival after hospital admission was much lower for patients with a respiratory hospitalization compared with those with a nonrespiratory hospitalization (median survival, 2.8 months [IQR, 0.63-16.2 months] vs 27.7 months [IQR, 7.4-59.6 months]; P = .0004). Multivariate analyses demonstrated that both all-cause and respiratory-related hospitalizations were strongly associated with mortality after adjusting for baseline demographics. Among patients with a respiratory hospitalization, 22.4% died while in the hospital, whereas 16.4% eventually went on to lung transplantation., Conclusions: Hospitalizations are common events in patients with IPF. Most hospitalizations are respiratory-related and are associated with high in-hospital mortality and limited survival beyond discharge. Both all-cause and respiratory hospitalizations are associated with mortality, and therefore, either could be used as an end point in IPF clinical trials. more...

Elevated interleukin-6 (IL-6) levels are associated with type 2 diabetes, but its role in glucose metabolism is controversial. We investigated the effect of IL-6 on insulin-stimulated glucose metabolism in type 2 diabetes patients and hypothesized that an acute, moderate IL-6 elevation would increase the insulin-mediated glucose uptake. Men with type 2 diabetes not treated with insulin [n = 9, age 54.9 ± 9.7 (mean ± SD) yr, body mass index 34.8 ± 6.1 kg/m(2), HbA1c 7.0 ± 1.0%] received continuous intravenous infusion with either recombinant human IL-6 (rhIL-6) or placebo. After 1 h with placebo or rhIL-6, a 3-h hyperinsulinemic-isoglycemic clamp was initiated. Whole body glucose metabolism was measured using stable isotope-labeled tracers. Signal transducer and activator of transcription 3 (STAT3) phosphorylation and suppressor of cytokine signaling 3 (SOCS3) expression were measured in muscle biopsies. Whole body energy expenditure was measured using indirect calorimetry. In response to the infusion of rhIL-6, circulating levels of IL-6 (P < 0.001), neutrophils (P < 0.001), and cortisol (P < 0.001) increased while lymphocytes decreased (P < 0.01). However, IL-6 infusion did not change glucose infusion rate, rate of appearance, or rate of disappearance during the clamp. While IL-6 enhanced phosphorylation of STAT3 in skeletal muscle (P = 0.041), the expression of SOCS3 remained unchanged. Whole body oxygen uptake (P < 0.01) and expired carbon dioxide (P < 0.01) increased during rhIL-6 infusion. In summary, although IL-6 induced local and systemic responses, the insulin-stimulated glucose uptake was not affected. While different contributing factors may be involved, our results are in contrast to our hypothesis and previous findings in young, healthy men. more...

Regular endurance exercise promotes metabolic and oxidative changes in skeletal muscle. Overexpression of interleukin-15 (IL-15) in mice exerts similar metabolic changes in muscle as seen with endurance exercise. Muscular IL-15 production has been shown to increase in mice after weeks of regular endurance running. With the present study we aimed to determine if muscular IL-15 production would increase in human male subjects following 12 weeks of endurance training. In two different studies we obtained plasma and muscle biopsies from young healthy subjects performing: (1) 12 weeks of ergometer cycling exercise five times per week with plasma and biopsies before and after the intervention, and (2) 3 h of ergometer cycling exercise with plasma and biopsies before and after the exercise bout and well into recovery. We measured changes in plasma IL-15, muscle IL-15 mRNA and IL-15 protein. Twelve weeks of regular endurance training induced a 40% increase in basal skeletal muscle IL-15 protein content (p < 0.01), but with no changes in either muscle IL-15 mRNA or plasma IL-15 levels. However, an acute bout of 3-h exercise did not show significant changes in muscle IL-15 or plasma IL-15 levels. The induction of muscle IL-15 protein in humans following a regular training period supports previous findings in mice and emphasizes the hypothesis of IL-15 taking part in skeletal muscle adaptation during training. more...

Type 2 diabetes is characterized by increased insulin resistance and impaired insulin secretion. Type 2 diabetes is also associated with low-grade inflammation and increased levels of proinflammatory cytokines such as TNF-α. TNF-α has been shown to impair peripheral insulin signaling in vitro and in vivo. However, it is unclear whether TNF-α may also affect endogenous glucose production (EGP) during fasting and glucose-stimulated insulin secretion (GSIS) in vivo. We hypothesized that low-dose TNF- α would increase EGP and attenuate GSIS. Recombinant human TNF-α or placebo was infused in healthy, nondiabetic young men (n = 10) during a 4-hour basal period followed by an intravenous glucose tolerance test (IVGTT). TNF-α lowered insulin levels by 12% during the basal period (P < 0.05). In response to the IVGTT, insulin levels increased markedly in both trials, but there was no difference between trials. Compared to placebo, TNF-α did not affect EGP during the basal period. Our results indicate that TNF-α acutely lowers basal plasma insulin levels but does not impair GSIS. The mechanisms behind this are unknown but we suggest that it may be due to TNF-α increasing clearance of insulin from plasma without impairing beta-cell function or hepatic insulin sensitivity. more...

Background: This study evaluated the hemostatic effectiveness and safety of Fibrin Pad (Omrix Biopharmaceuticals Ltd.) vs absorbable hemostat in patients undergoing nonemergent surgery. Fibrin Pad is a topical absorbable hemostat designed to be effective in a variety of soft tissues and across multiple bleeding intensities., Study Design: Patients 18 years and older, requiring abdominal, retroperitoneal, pelvic, or thoracic (noncardiac) surgery and with an appropriate soft-tissue target bleeding site (TBS), were randomized to receive Fibrin Pad or absorbable hemostat (NCT00658723). Patients were stratified by bleeding severity at the TBS. Assessments included percentage of patients achieving hemostasis at 4 minutes after randomization with no rebleeding requiring treatment during the subsequent 6 minutes (primary endpoint), proportion of patients achieving hemostasis at 10 minutes, and incidence of treatment failure., Results: On the primary endpoint, 98.3% of patients with Fibrin Pad and 53.3% with absorbable hemostat achieved hemostasis at 4 minutes (p < 0.0001). The treatment differential was magnified (efficacy was maintained with Fibrin Pad but decreased with absorbable hemostat) with increasing bleeding intensity: in patients with mild bleeding, 100.0% vs 80.0% achieved hemostasis with Fibrin Pad and absorbable hemostat (p = 0.03), respectively; rates were 96.6% vs 26.7%, respectively (p < 0.0001) with moderate bleeding. Percentages of patients who achieved hemostasis at 10 minutes were: Fibrin Pad, 98.3% and absorbable hemostat, 73.3% (p < 0.0001). Incidences of adverse events were comparable between groups., Conclusions: Fibrin Pad is superior to absorbable hemostat (SURGICEL Original Absorbable Hemostat [Ethicon]) in soft-tissue bleeding control and is safe and effective as an adjunct for rapidly and reliably achieving hemostasis for soft-tissue bleeding during surgery., (Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.) more...

Background: Plasma follistatin is elevated in patients with low-grade inflammation and insulin resistance as observed with polycystic ovary syndrome. In the present study, we evaluated plasma follistatin in patients with type 2 diabetes characterised by low-grade inflammation and assessed the acute effects of hyperglycemia, hyperinsulinemia and LPS on plasma follistatin., Methods: Baseline plasma follistatin and inflammatory biomarkers were measured in a cross-sectional study that involved 95 patients with type 2 diabetes and 103 matched controls. To determine the acute effect of hyperglycemia and hyperinsulinemia on follistatin, hyperglycemic and hyperinsulinemic-euglycemic clamps were performed in five healthy males. Furthermore, 15 patients with type 2 diabetes and 22 healthy controls were challenged with low-dose LPS to determine the effect on follistatin., Results: Patients with type 2 diabetes have higher HOMA2-IR values mean [95% CI] 1.64 [1.40-1.93] versus mean 0.86 [0.75-0.99], p < 0.001 and inflammatory markers compared with controls. Baseline plasma follistatin is elevated in patients with type 2 diabetes compared with controls mean 1564 [1456-1680] versus mean 1328 [1225-1440] ng/L, p = 0.003 and correlates with fasting glucose levels (r = 0.44, p < 0.0001), 2 h glucose (r = 0.48, p < 0.0001), HbA1c (r = 0.41, p < 0.0001), triacylglycerol (r = 0.28, p = 0.008) and total cholesterol (r = 0.33, p = 0.004) in patients but not in controls. No correlation exists between plasma follistatin and inflammatory biomarkers in either of the groups. Neither hyperglycemia, hyperinsulinemia nor LPS increase plasma follistatin., Conclusions: Plasma follistatin is moderately elevated in patients with type 2 diabetes. Our findings suggest that this is not likely caused by hyperglycemia, hyperinsulinemia or systemic low-grade inflammation., (Copyright © 2013 John Wiley & Sons, Ltd.) more...

Background: The course of idiopathic pulmonary fibrosis (IPF) is characterized by variable patterns of disease progression. The red cell distribution width (RDW) is a parameter that is routinely reported with all CBC counts. We sought to test the prognostic usefulness of this parameter in a well-defined cohort of patients with IPF., Methods: CBCs, demographics, and pulmonary function data from patients with IPF evaluated between January 1997 and June 2011 were collated. Patient outcomes were ascertained from the program's database and the Social Security Death Index., Results: There were 319 patients with IPF evaluated in whom baseline CBCs were available. The range in the RDW was 11.9 to 21.9 (median 14.1). There were 228 subjects with RDW values ≤ 15 (normal) and 91 patients with RDW values &gt; 15. Patients with normal RDW values had a median survival of 43.1 months compared with 16.3 months for those whose RDW was &gt; 15 (P = .001). There were 198 patients with available serial RDW data. Those patients who had a change in the RDW of less or greater than +0.010/mo had median survivals of 43.0 and 23.9 months, respectively (P = .0246)., Conclusions: The RDW is a readily available laboratory test result that may provide important, independent prognostic information at baseline and follow-up in patients with IPF. Further studies are warranted to validate this as a biomarker for IPF outcomes, as well as to define the biologic basis for this association. more...

Aims/hypothesis: Soluble CD163 (sCD163) was recently identified as a strong risk marker for developing type 2 diabetes. We hypothesised that sCD163 independently associates with insulin resistance., Methods: This cross-sectional study includes 234 participants: 96 with type 2 diabetes, 34 with impaired glucose tolerance (IGT) and 104 with normal glucose tolerance (NGT), matched for sex and BMI. Glucose-lowering medication was paused for 1 week before plasma samples were obtained for determination of sCD163 and other inflammatory and metabolic variables. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-IR)., Results: Concentrations of sCD163 were 1.95 mg/l (0.63-6.97) in individuals with type 2 diabetes, 1.64 mg/l (0.58-4.19) in those with IGT, and 1.48 mg/l (0.48-4.11) (median [range]) in those with NGT (p < 0.0001). In univariate analyses, sCD163 correlated significantly with HOMA-IR (R = 0.44), insulin (R = 0.41), glucose (R = 0.30), triacylglycerol (R = 0.29) and HDL-cholesterol (R = -0.34) (all p < 0.0001). All but glucose remained significant when adjusting for age, sex, BMI and glycaemic group. In univariate regression analyses, HOMA-IR was associated with sCD163, C-reactive protein (CRP), TNF-α and IL-6 (all p ≤ 0.0001). An increase of 50% in sCD163 resulted in an estimated increase in HOMA-IR of 36% (95% CI 26, 48; p < 0.0001). In multiple linear regression analyses, sCD163 (p = 0.001) and CRP (p = 0.01) remained independent predictors of HOMA-IR, whereas TNF-α and IL-6 did not., Conclusions/interpretation: Macrophage-specific sCD163 was strongly associated with insulin resistance independently of TNF-α and other predictors. Moreover, sCD163 was associated with well-known variables of the metabolic syndrome. more...

Vitamin C and E supplementation has been shown to attenuate the acute exercise-induced increase in plasma interleukin-6 (IL-6) concentration. Here, we studied the effect of antioxidant vitamins on the regulation of IL-6 expression in muscle and the circulation in response to acute exercise before and after high-intensity endurance exercise training. Twenty-one young healthy men were allocated into either a vitamin (VT; vitamin C and E, n = 11) or a placebo (PL, n = 10) group. A 1-h acute bicycling exercise trial at 65% of maximal power output was performed before and after 12 wk of progressive endurance exercise training. In response to training, the acute exercise-induced IL-6 response was attenuated in PL (P < 0.02), but not in VT (P = 0.82). However, no clear difference between groups was observed (group × training: P = 0.13). Endurance exercise training also attenuated the acute exercise-induced increase in muscle-IL-6 mRNA in both groups. Oxidative stress, assessed by plasma protein carbonyls concentration, was overall higher in the VT compared with the PL group (group effect: P < 0.005). This was accompanied by a general increase in skeletal muscle mRNA expression of antioxidative enzymes, including catalase, copper-zinc superoxide dismutase, and glutathione peroxidase 1 mRNA expression in the VT group. However, skeletal muscle protein content of catalase, copper-zinc superoxide dismutase, or glutathione peroxidase 1 was not affected by training or supplementation. In conclusion, our results indicate that, although vitamin C and E supplementation may attenuate exercise-induced increases in plasma IL-6 there is no clear additive effect when combined with endurance training. more...

Up to 50% of the over 140,000 new colorectal cancer patients will present with synchronous colorectal cancer and liver metastasis. Surgical management of patients with resectable synchronous colorectal hepatic metastasis is complex and must consider multiple factors, including the presence of symptoms, location of primary tumor and liver metastases, extent of tumor (both primary and metastatic), patient performance status, and underlying comorbidities. Possible approaches to this select group of patients have included a synchronous resection of the colorectal primary and the hepatic metastases or a staged resection approach. The available literature regarding the safety of synchronous versus staged approaches confirms that a simultaneous resection may be performed in selected patients with acceptable morbidity and mortality. Perioperative mortality when minor hepatectomies are combined with colorectal resection is consistently ≤5%. Perioperative morbidity varies considerably following both synchronous and staged resections. However, the bulk of the existing literature confirms that simultaneous resections are both feasible and safe when hepatic resections are limited to <3 segments. Data regarding the oncologic outcomes following synchronous versus staged resections for Stage IV colorectal cancer are more limited than those available regarding postoperative morbidity and mortality. The available data suggest equivalent overall and disease-free survival regardless of timing of resection. Experience with minimally invasive combined colorectal and hepatic resections is extremely limited to date and consists exclusively of small single center series. The potential benefits of a minimally invasive approach will await the results of larger studies. more...